First-in-class signal-interfering (siDNA) product candidate, AsiDNA breaks the cycle of tumor DNA repair by interfering at the core of DNA damage, blocking multiple repair pathways, while sparing healthy cells. AsiDNA and its technology originate from three major French academic centers: Curie Institute, CNRS, and the Museum of Natural History. It offers a potential new treatment option for patients suffering from various types of cancer.
DNA damages of cancer cells are caused by cytotoxics (chemo- and radiotherapies) or occur spontaneously in the case of certain genetically unstable tumors. Cancer cells have the ability to recognize DNA damage and activate multiple repair pathways or proteins to survive DNA damages. Approaches to prevent DNA repair mechanisms have been identified as one of the most promising new avenues in cancer treatment.
AsiDNA is a short double-stranded DNA molecule that acts as a decoy, mimicking double-strand breaks in the cell’s native DNA. When introduced into a cell, AsiDNA molecules trigger false DNA break signals to activate and attract DNA repair proteins, which prevents the recruitment of repair enzymes to the site of actual DNA damage. As a result, the damage of a cell’s native DNA remains unrepaired. As cancer cells have lost the ability to regulate cell division, they will continue dividing with damaged DNA, ultimately leading to cancer cell death (mitotic death). Healthy cells, on the other hand, will halt cell division until the compound is no longer present and damaged DNA can be repaired.
This approach is significantly differentiated from others in the field as it does not inhibit specific enzymes (such as the PARP-inhibitors) but targets the entire DNA repair system.
A first-in-human Phase I/IIa trial performed in metastatic melanoma demonstrated that the siDNA molecules showed good tolerance and safety when administered intra-tumorally and subcutaneously around the tumors.
Onxeo plans to initate the development of the product by the systemic route, and to assess safety and tolerance in monotherapy and in combination with other DNA-damaging agents in various solid tumors. This clinical development will be implemented after first optimizing the manufacturing process.View press releases View publications
Dna repair and cancer treatment